Morphometric analysis of corneal endothelium following radial keratotomy

We performed morphometric analysis of the central corneal endothelium on 24 eyes of 19 patients who had had anterior radial keratotomy. The endothelium was analyzed for a variety of parameters, including cell area, perimeter, side lengths, cell shape, and number of sides. Mean, standard deviation, and coefficient of variation were calculated for each parameter. The mean cell density decreased from 2,835 to 2,677 cells/mm2, mean cell perimeter increased from 71.4 micron to 74.3 micron, and mean side length increased from 11.8 micron to 12.3 micron following surgery. The changes in these three parameters were statistically significant (P less than 0.05). The coefficient of variation of cell area (polymegathism) changed from 0.319 to 0.307, the hexagonality changed from 62.5% to 59.6%, and the cell shape changed from 0.872 to 0.867. The changes in these parameters were not statistically different before and after surgery. The group of patients that had no reported microperforations showed only a small decrease of cell density (1.6%), while the group of patients that had microperforations showed a large decrease of cell density (14.3%). The cell perimeter and side lengths showed a similar pattern. The group of corneas with the optical zone diameter less than 3.5 mm showed a decrease in mean cell density from 2,994 to 2,725 cells/mm2, and the cell shape changed from 0.874 to 0.866 following surgery. The changes in these parameters were statistically significant (P less than 0.05) before and after surgery. Among all factors associated with radial keratotomy, microperforation and a small diameter of central optical zone appear to be the two greatest risk factors.     

Cocoa procyanidins inhibit expression and activation of MMP-2 in vascular smooth muscle cells by direct inhibition of MEK and MT1-MMP activities

AIMS: Expression and activation of matrix metalloproteinase (MMP)-2 play pivotal roles in the migration and invasion of human aortic vascular smooth muscle cells (VSMC) originating from normal human tissue, which is strongly linked to atherosclerosis. The present study investigated the possible inhibitory effects of cocoa procyanidin on thrombin-induced expression and activation of MMP-2 in VSMC. METHODS AND RESULTS: Cocoa procyanidin fraction (CPF) and procyanidin B2, one of major procyanidins in cocoa (3 microg/mL and 5 microM, respectively), strongly inhibited thrombin-induced activation and expression of pro-MMP-2 in VSMC, as determined by zymography. The thrombin-induced invasion and migration of VSMC were inhibited by CPF or procyanidin B2 (P < 0.05), as assessed by a modified Boyden chamber and wound healing assays, respectively. An enzymatic assay data demonstrated that CPF and procyanidin B2 directly inhibited membrane type-1 (MT1)-MMP activity (P < 0.05), and this inhibition of CPF was greater than those of red wine polyphenols. Western blot data showed that CPF and procyanidin B2 inhibited thrombin-induced phosphorylation of extracellular signal-regulated protein kinase but not mitogen-activated protein kinase kinase (MEK) in VSMC. Kinase and pull-down data revealed that CPF and procyanidin B2 inhibited MEK1 activity and directly bound with glutathione-S-transferase-MEK1. In addition, the thrombin-induced invasion and migration and the activation and expression of pro-MMP-2 in VSMC were attenuated by U0126 (a well-known inhibitor of MEK1). CONCLUSION: Cocoa procyanidins are potent inhibitors of MEK and MT1-MMP, and subsequently inhibit the expression and activation of pro-MMP-2, and also the invasion and migration of VSMC, which may in part explain the molecular action of antiatherosclerotic effects of cocoa.     

Anti-allergic prenylated flavonoids from the roots of Sophora flavescens

The bioassay-guided fractionation of the MeOH extract from the root of Sophora flavescens led to the isolation of eight known prenylated flavonoids ( 1 - 8) responsible for the IN VITRO anti-allergic activity. Among them, kushenol N ( 3), sophoraflavanone G ( 6), and leachianone A ( 7) demonstrated significant inhibition of the release of beta-hexosaminidase from cultured RBL-2H3 cells with IC (50) values ranging from 15 to 30 muM.     

Ex Vivo Culture Models of Hidradenitis Suppurativa for Defining Molecular Pathogenesis and Treatment Efficacy of Novel Drugs

Inflammation - Hidradenitis suppurativa (HS) is a complex and debilitating&nbsp;inflammatory skin disease for which no effective treatment is available currently. This is partly because of the...     

Autoantibody epitopes to the smaller isoform of glutamate decarboxylase do not differ in Swedish and Japanese type 1 diabetes patients and may be associated with high-risk human leucocyte antigen class II alleles

Type 1 diabetes (T1D) is an autoimmune disease with a strong human leucocyte antigen (HLA) class II association. Depending on geographic locations, the disease-associated HLA class II alleles vary. We evaluated the beta cell-specific autoimmunity reflected in autoantibodies directed to the smaller isoform of glutamate decarboxylase (GAD65) in Japanese and Swedish T1D patients. GAD65Ab epitope specificities were assessed using GAD65-specific recombinant Fab. GAD65Ab epitope specificities did not differ between Swedish and Japanese patients. Only recognition of the MICA-4-defined middle epitope was significantly stronger in the Japanese T1D patient group compared to the Swedish T1D patients (P = 0.001). Binding to the b96.11-defined middle epitope was substantial in both groups and showed significant associations with high-risk HLA class II haplotypes. In the Japanese T1D group the association was with haplotype DRB1*0802-DQB1*0302 (P = 0.0008), while in the Swedish T1D patients binding to the b96.11-defined epitope as associated with the presence of high-risk HLA genotypes DR3-DQB1*0201 and/or DR4-DQB1*0302 (P = 0.02). A significant association between reduction in binding in the presence of recombinant Fab (rFab) DPD and high-risk allele DQB1*0201 was found (P = 0.008) in the Swedish T1D patients only. We hypothesize that epitope-specific autoantibodies effect the peptide presentation on HLA class II molecules by modulating antigen uptake and processing. Molecular modelling of the high-risk HLA class II molecules will be necessary to test whether these different molecules present similar peptide-binding specificities.     

Titanium Dioxide Exposure Induces Acute Eosinophilic Lung Inflammation in Rabbits

Titanium dioxide (TiO₂) is increasingly widely used in industrial, commercial and home products. TiO₂ aggravates respiratory symptoms by induction of pulmonary inflammation although the mechanisms have not been well investigated. We aimed to investigate lung inflammation in rabbits after intratracheal instillation of P25 TiO₂. One ml of 10, 50 and 250 µg of P25 TiO₂ was instilled into one of the lungs of rabbits, chest computed-tomography was performed, and bronchoalveolar lavage (BAL) fluid was collected before, at 1 and 24 h after P25 TiO₂ exposure. Changes in inflammatory cells in the BAL fluids were measured. Lung pathological assay was also carried out at 24 h after P25 TiO₂ exposure. Ground glass opacities were noted in both lungs 1 h after P25 TiO₂ and saline (control) instillation. Although the control lung showed complete resolution at 24 h, the lung exposed to P25 TiO₂ showed persistent ground glass opacities at 24 h. The eosinophil counts in BAL fluid were significantly increased after P25 TiO₂ exposure. P25 TiO₂ induced a dose dependent increase of eosinophils in BAL fluid but no significant differences in neutrophil and lymphocyte cell counts were detected. The present findings suggest that P25 TiO₂ induces lung inflammation in rabbits which is associated with eosinophilic inflammation.     

Early experience with thoracoscopic repair of congenital diaphragmatic hernias in pediatric age group: results and lessons learned

Purpose  

To describe the surgical technique, initial results, and overview indications of thoracoscopic repair of congenital diaphragmatic hernia.     

Epidemiology and clinical characteristics of Clostridium difficile infection in a Korean tertiary hospital

In order to investigate the incidence, clinical and microbiologic characteristics of Clostridium difficile infection (CDI) in Korea, a prospective observational study was performed. From September 2008 through January 2010, all patients whose stool was tested for toxin assay A&B and/or C. difficile culture were studied for clinical characteristics. Toxin types of the isolates from stool were tested. The mean incidence of CDI per 100,000 patient-days was 71.6 by month (range, 52.5-114.0), and the ratio of CDI to antibiotic-associated diarrhea was 0.23. Among 200 CDI patients, 37.5% (75/200) was severe CDI based on severity score. Clinical outcome of 189 CDI was as followed; 25.9% (49/189) improved without treatment, 84.3% (118/140) achieved clinical cure and attributed mortality was 0.7% (1/140) with the treatment. Recurrence rate was 21.4% (30/140) and cure without recurrence was 66.4% (93/140). The most common type of toxin was toxin A-positive/toxin B-positive strain (77.5%), toxin A-negative/toxin B-positive strains or binary toxin-producing strains comprised 15.4% or 7.1%, respectively. In conclusion, the incidence of CDI in Korea is a little higher than other reports during the non-epidemic setting. We expect that the change of epidemiology and clinical severity in CDI can be evaluated based on these results.